Interactions of insulin-mimetic zinc(II) complexes with cell constituents: glutathione and ATP

Enyedy, Éva Anna and Károlyné Lakatos, Andrea and Horváth, László and Kiss, Tamás (2008) Interactions of insulin-mimetic zinc(II) complexes with cell constituents: glutathione and ATP. JOURNAL OF INORGANIC BIOCHEMISTRY, 102 (7). pp. 1473-1485. ISSN 0162-0134

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Abstract

Ternary complex formation of some potent insulin–mimetic zinc(II) complexes of bidentate ligands: maltol and 3-hydroxy-1,2- dimethyl-pyridinone with (O,O), 2-picolinic acid and 6-methylpicolinic acid with (N,O) and the tridentate 2,6-dipicolinic acid with(O,N,O) coordination modes was studied in aqueous solutions by pH-potentiometry and spectroscopic (UV, CD, ESI-MS) methodsin the presence of critical cell constituents such as L-glutathione reduced (GSH) and adenosine 50-triphosphate (ATP). Results showed that formation of the ternary complexes was hindered in the case of 2,6-dipicolinic acid, especially with ATP, while it was favoured with the bidentate ligands in the physiological pH range. Driving force of the formation of mixed-ligand species was found to be a more enhanced coordination of GSH and ATP as second ligands in the ternary complexes than in their binary ones due to steric and electrostatic reasons. The mitochondrial dehydrogenase activity of the zinc(II) complexes, as an indirect indicator for the glucose intake, was measured on Mono Mac and 3T3-L1 adipocyte cell lines. The activity of the complexes up to 10–100 lM concentration was in the range of the effect of 0.75–1.5 lM insulin, while at higher concentration it was broken down due to the sensitivity of the cells to toxicity of the complexes.

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